Method for producing n-phosphonomethyl iminodiacetic acid

ABSTRACT

The present invention relates to a process for the preparation of N-phosphonomethyliminodiacetic acid by reacting an alkali metal salt of iminodiacetic acid with phosphorus trichloride in aqueous solution with formation of the hydrochloride of iminodiacetic acid, phosphorous acid and of the corresponding alkali metal chloride, followed by reaction with a formaldehyde source and, if desired, recovery of the N-phosphonomethyliminodiacetic acid from the reaction mixture, in which water, which may comprise HCl, is removed from the reaction mixture during and/or after reacting the alkali metal salt of iminodiacetic acid with phosphorus trichloride until the concentration of iminodiacetic acid hydrochloride is at least 40% by weight, based on the weight of the reaction mixture minus the weight of alkali metal chloride. 
     The process makes possible the preparation of N-phosphonomethyliminodiacetic acid in a simple fashion and in high yield.

The invention relates to a process for the preparation ofN-phosphonomethyliminodiacetic acid (PMIDA) by reacting an alkali metalsalt of iminodiacetic acid (IDA) with phosphorus trichloride in aqueoussolution with formation of the hydrochloride of iminodiacetic acid,phosphorous acid and of the corresponding alkali metal chloride,followed by reaction with a formaldehyde source.

As is known, PMIDA is an intermediate for the preparation of thenonselective herbicide N-phosphonomethylglycine (glyphosate). A numberof processes for the preparation of PMIDA by phosphonomethylation of IDAhave already been described. Some of these processes start from IDA inthe form of the free acid. Thus, DE 2914294 A discloses the reaction ofIDA with phosphorus trichloride and formaldehyde. This leads to arelatively high yield. However, the disadvantage of the process is thata large excess of phosphorus trichloride and formaldehyde must beemployed. WO 94/15939 describes the reaction of IDA with phosphorousacid and a formaldehyde source in aqueous solution in the presence ofconcentrated sulfuric acid. In order to obtain satisfactory yields, thefiltrates obtained in the recovery of PMIDA are subjected to complicatedwork-up.

EP 618212 A (which corresponds to U.S. Pat. No. 5,312,973) describes thepreparation of PMIDA by phosphonomethylation of IDA with an aqueoussolution of phosphoric acid and hydrochloric acid, and alsoformaldehyde. This aqueous solution is prepared before thephosphonomethylation by hydrolyzing phosphorus trichloride with water orhydrochloric acid, the reaction temperature and the amount of waterbeing regulated in such a way that hydrochloric acid and phosphorousacid are present in the aqueous solution in a molar ratio of 0.5:1 to2:1. The process is thus carried out with substoichiometric amounts ofhydrochloric acid. Furthermore, the phosphonomethylation is carried outin such a way that IDA and phosphorous acid are present in a molar ratioof between 1:1 and 1:1.2. This complicated and tedious process givesPMIDA in a yield of 91%.

Other processes start from an alkali metal salt, in particular thedisodium salt (DSIDA) of IDA. Thus, WO 96/40698 (which corresponds toU.S. Pat. No. 5,688,994) describes a process for the preparation ofPMIDA by simultaneously introducing an IDA source, a formaldehyde sourceand a source for phosphorous acid into the reaction mixture. Substanceswhich can be used as IDA source are an alkali metal salt or the salt ofa strong mineral acid of IDA or IDA in the form of the free acid. Theyield of 87% achieved in this process is not satisfactory.

EP 595598 A describes the preparation of hydroxymethyliminodiacetic acidby reacting an alkali metal salt of IDA with a formaldehyde source. Thisis followed by the reaction of the resulting hydroxymethyliminodiaceticacid with phosphorous acid in the presence of hydrochloric acid. Theroute via hydroxymethyliminodiacetic acid as intermediate was chosen inorder to obtain a storage-stable starting solution for the preparationof PMIDA. In contrast to hydroxymethyliminodiacetic acid, the disodiumsalt of IDA precipitates upon storage in the form of crystals and causesdifficulties upon subsequent processing.

WO 00/14093 describes a process for the preparation of PMIDA by reactinga metal salt of IDA with such an amount of a mineral acid which isrequired for the formation of IDA, addition of a source for phosphorousacid in order to obtain a solution of the phosphite salt of IDA,separation of the metal salt present in the reaction mixture of thestrong mineral acid used for forming IDA from the solution of thephosphite salt of iminodiacetic acid, and phosphonomethylation of thephosphite salt with a source for phosphorous acid and a formaldehydesource in the presence of a strong mineral acid. While this processgives a relatively high yield, it is complicated because it encompassestwo additional reaction steps, viz. the formation of the phosphite saltof IDA, and the separation of the abovementioned metal salt. A similarprocess is described in WO 00/22888.

Finally, EP 155926 A (which corresponds to U.S. Pat. Nos. 4,724,103 and4,775,498) describes a process for the preparation of PMIDA by reactingan alkali metal salt of IDA with a strong mineral acid with formation ofthe mineral acid salt of IDA, followed by phosphonomethylation withformaldehyde and phosphorous acid. Phosphorous acid and hydrochloricacid, being a strong mineral acid, can be provided by hydrolyzingphosphorus trichloride. Following the phosphonomethylation, aqueous NaOHis added to the reaction mixture in order to dissolve off the alkalimetal salt of the strong mineral acid, which salt is present in thereaction mixture, so that PMIDA can be obtained as precipitate. Theyield achieved with this process is not satisfactory.

DE 19909200 describes a process for the preparation of PMIDA by reactingIDA with phosphorous acid and formaldehyde in aqueous solution in thepresence of a strong mineral acid. The reaction is carried out at atemperature of 110–150° C. and under protective gas atmosphere.

Further processes for the preparation of PMIDA are described in GB2154588 A and U.S. Pat. No. 3,288,846.

The processes described in the prior art share the fact that they arecomplicated, for example because they encompass additional reactionsteps, such as neutralization of the alkali metal salt of IDA, and/orthat the yields leave something to be desired.

It is an object of the present invention to provide a process whichyields PMIDA in a simple fashion and in high yield.

We have found that this object is achieved when water, which maycomprise HCl, is removed from the reaction mixture during and/or afterreacting an alkali metal salt of IDA with phosphorus trichloride untilthe IDA·HCl concentration is at least 44% by weight.

The invention therefore relates to a process for the preparation ofN-phosphonomethyliminodiacetic acid by reacting an alkali metal salt ofiminodiacetic acid with phosphorus trichloride in aqueous solution withformation of the hydrochloride of iminodiacetic acid, phosphorous acidand of the corresponding alkali metal chloride, followed by reaction ofthe reaction product with a formaldehyde source, in which water, whichmay comprise HCl, is removed from the reaction mixture during and/orafter reacting the alkali metal salt of IDA with phosphorus trichlorideuntil the concentration of iminodiacetic acid hydrochloride is at least44% by weight, based on the weight of the reaction mixture minus theweight of alkali metal chloride, and, if desired, theN-phosphonomethyliminodiacetic acid is recovered from the reactionmixture.

The process according to the invention can be illustrated by thefollowing equation, the disodium salt having been selected as the alkalimetal salt of IDA:

Substances which are used as the alkali metal salt of IDA are, inparticular, the disodium and the dipotassium salts. The salts ofiminodiacetic acid are usually prepared by hydrolyzingiminodiacetonitrile. The hydrolysate obtained can be employed asstarting material for the process according to the invention. As analternative, a salt which originates from other sources may also beemployed. It is particularly preferred to employ the alkali metal saltof IDA in a purity of at least 90%.

In general, the alkali metal salt of IDA is employed in aqueous solutionin a concentration of from 30 to 50% by weight, in particular from 35 to45% by weight.

Phosphorus trichloride is added to the aqueous soluton of the alkalimetal salt of IDA. The phosphorus trichloride hydrolyzes with formationof phosphorous acid and HCl, the latter of which reacts with the alkalimetal salt of IDA with formation of the hydrochloride of IDA and of thecorresponding alkali metal chloride. Phosphorus trichloride ispreferably used in an amount of from approximately 1 to 1.2 molarequivalents (based on the alkali metal salt of IDA). When using morethan one molar equivalent, excess HCl forms, which remains dissolved inthe aqueous phase.

During and/or after the reaction of the alkali metal salt of IDA withphosphorus trichloride, water is removed from the reaction mixture, inparticular by distillation under atmospheric pressure or reducedpressure (approximately 0.1 to 0.8 bar). When using more than one molarequivalent of phosphorus trichloride, the water which is removed fromthe reaction mixture comprises HCl. The water is preferably removedmaking use of the heat of the reaction of phosphorus trichloride withwater. This reaction is strongly exothermic, and the heat of reactionwhich is given off suffices to halt the reaction mixture at the boil(under atmospheric pressure) and to remove the desired amount of waterby distillation. As an alternative, at least some of the water can beremoved by distillation after hydrolysis.

Since the phosphonomethylation which follows is carried out in thepresence of acid, a strong mineral acid, in particular hydrochloricacid, can be added after the water has been removed. It is expedient touse an acid at a higher concentration, for example ≧20% by weightstrength hydrochloric acid, in particular concentrated hydrochloric acid(30–37% by weight strength). The hydrochloric acid concentration in thereaction mixture prior to reaction with the formaldehyde sourcepreferably amounts to 5 to 20% by weight, based on the amount by weightof water in the reaction mixture.

In accordance with the invention, such an amount of water is removedthat the concentration of IDA·HCl in the reaction mixture before thephosphonomethylation is at least 40% by weight, based on the weight ofthe reaction mixture minus the weight of alkali metal chloride.Preferably, the concentration of IDA·HCl is in the range of from 44 to55% by weight.

The phosphonomethylation is effected by reacting IDA·HCl withphosphorous acid and a formaldehyde source in the presence of acid. Thepurpose of the acid is to minimize the formation ofN-methyliminodiacetic acid as by-product.

The formaldehyde source used is in particular an aqueous formaldehydesolution at a concentration of 30 to 50% by weight. As an alternative,paraformaldehyde may be used. It is preferred to use approximately 1.1to 1.5 molar equivalents of formaldehyde. Using phosphorus trichloridein essentially equimolar amounts and the formaldehyde source in such anamount that approximately 1.3 to 1.45 molar equivalents of formaldehydeare available has proved to be particularly preferred.

In general, the reaction temperature is in the range of fromapproximately 85° C. to approximately 180° C., preferably fromapproximately 105 to approximately 145° C., and in particular fromapproximately 125 to approximately 145° C. The reaction can be carriedout under atmospheric pressure or under moderate superatmosphericpressure, for example approximately 1.1–3 bar, either in the air orunder protective gas.

Adding the formaldehyde source in two portions has proved to beparticularly advantageous. First, most of the formaldehyde source, inparticular 60 to 90% by weight, preferably 75 to 85% by weight, isadded, while the remainder is added after a reaction time ofapproximately one hour. The overall reaction time generally amounts to1.5 to 5 hours, in particular 2 to 3 hours. After phosphonomethylation,a suspension is present. In order to precipitate PMIDA and to dissolvethe suspended alkali metal chloride, aqueous NaOH is added until thealkali metal chloride is in dissolved form. To precipitate PMIDA, a baseis added to the solution up to not more than the isoelectric point (pH1.3). Preferably, however, the pH is brought to a value of below theisoelectric point, in particular to a value in the range of from 0 to 1,preferably from 0.5 to 0.8. Surprisingly, it has emerged that thesolubility of PMIDA is lower below the isoelectric point, the yield thusbeing increased.

The base used is an alkali metal hydroxide or alkaline earth metalhydroxide, preferably sodium hydroxide, in particular 15–25% by weightof aqueous sodium hydroxide solution. In order to obtain yields whichare as high as possible, the pH is established, and/or thecrystallization is effected, at as low a temperature as possible, forexample at a temperature in the range of from 5° C. to 20° C.

The PMIDA which has separated out is recovered in the customary fashion,for example by filtration. If desired, the filter cake is washed withwater.

Despite adjusting the pH and working at a low temperature duringprecipitation and crystallization, as mentioned above, a small amount ofthe PMIDA remains in the mother liquor and the wash water. This residualPMIDA can be recovered in the customary fashion, for example byevaporating the mother liquor and the wash water to dryness.

The process according to the invention can be carried out in customaryreactors either continuously, semicontinuously or batchwise. If desired,the process can be carried out under protective gas atmosphere, forexample under nitrogen or argon.

The process according to the invention has the advantage that PMIDA canbe prepared in a simple fashion and in high yield. Nevertheless, thestarting materials are employed only in a small molar excess. Thestarting materials can be employed in high concentration, and thesuspension formed during the reaction of the alkali metal salt of IDAwith phosphorus trichloride can still be handled with ease, despite theconcentrated operation.

The examples which follow illustrate the invention without imposing anylimitation.

EXAMPLE 1

554 g of water are introduced into a 1.6 l reactor equipped with turbineagitator (950 rpm) and baffle of the agitator. First, 203 g of NaOH(5.08 mol) and then 338 g of IDA (2.54 mol) are added with stirring andthe mixture is refluxed, giving rise to a clear solution (disodium saltof iminodiacetic acid). This corresponds to 1095 g of a 41% strengthsolution of DSIDA in water. 348 g (2.54 mol) of PCl₃ are added in thecourse of one hour under reflux via a glass tube which is tapered towardthe bottom and projects under the surface of the reaction mixture. Therefluxing mixture is pumped into a 1.6 l stirred vessel equipped withimpeller agitator (950 rpm) and baffle of the agitator and flushed with50 g of H₂O. 411 g of a 2.8% strength HCl are distilled off from thereaction mixture. 194 g of 37% strength HCl are subsequently added tothe reaction mixture, and 216 g of 49% strength formalin (3.55 mol) aremetered below the surface of the reaction mixture in the course of onehour under reflux. Stirring is then continued for two hours under refluxand the contents of the reactor are transferred to a 2 l reactorequipped with a three-level cross-arm agitator (330 rpm) and precooledto a jacket temperature of 10° C. When the suspension has cooled to 26°C., 627 g of 20% strength NaOH (3.73 mol) are metered in under thesurface of the reaction mixture in the course of 25 minutes so that thepH is 0.8. The suspension is pumped into a 2 l reactor equipped withanchor agitator (220 rpm), and stirring is continued for one hour at 15°C. The suspension is filtered through a glass-filter frit and washedwith 250 g of H₂O. The PMIDA, which contains residual moisture, is driedin a vacuum drying oven at 80° C. and 50 mbar. The solid hold-up in thereactors is isolated by washing with 3320 g of 1.5% strength NaOH. ThePMIDA content in the PMIDA crystallizate, in the wash solution, themother liquor and the wash water is determined by means of HPLC. 541 g(2.38 mol) of PMIDA are obtained in total, which corresponds to a totalyield of 94%. Of this, 4 g of PMIDA are present in the mother liquor and1 g of PMIDA in the wash water. The total yield minus the PMIDA lossesin the mother liquor and the wash water are defined as the isolatedyield. It amounts to 93%.

Examples 2 to 5 which follow were carried out in a similar fashion, butusing different amounts of starting materials and differentconcentrations. The results obtained are compiled in the table whichfollows.

g of 49% g of 37% Exam- g of strength strength Conc.^(a)) Total Isolatedple PCl₃ formalin Distilled off HCl added IDA * HCl yield yield 2 402184 323 g of 5.0% — 47% 94% 92% strength HCl 3 384 184 434 g of 4.0% —54% 95% 92% strength HCl 4 384 216 301 g of 6.7% 47.7 44% 91% 90%strength HCl 5 348 216 431 g of 2.8% 200 45% 93% 91% strength HCl 6 348216 412 g of 1.8% 200 44% 93%   88%^(b)) strength HCl ^(a))calculatedwithout NaCl ^(b))too much PMIDA in the mother liquor owing tosuperneutralization

1. A process for the preparation of N-phosphonomethyliminodiacetic acid,comprising a) reacting an alkali metal salt of iminodiacetic acid withphosphorus trichloride in aqueous solution to obtain the hydrochlorideof iminodiacetic acid, phosphorous acid and the corresponding alkalimetal chloride, b) halting the reaction mixture at the boil by theexothermic reaction of the phosphorous trichloride with water andremoving a sufficient amount of water from the reaction mixture untilthe concentration of iminodiacetic acid hydrochloride is 44 to 55% byweight, based on the weight of the mixture minus the weight of alkalimetal chloride, c) reacting with a formaldehyde source, and d)recovering the N-phosphonomethyliminodiacetic acid thus formed from thereaction mixture.
 2. A process as claimed in claim 1, wherein the amountof HCl in the reaction mixture before the reaction with the formaldehydesource is brought to 5 to 20% by weight, based on the amount by weightof water in the reaction mixture.
 3. A process as claimed in claim 1,wherein approximately 1.0 to 1.2 molar equivalents of phosphorustrichloride are used.
 4. A process as claimed in claim 1, wherein theformaldehyde source is employed in such an amount that 1.0 to 1.5 molarequivalents of formaldehyde are available.
 5. A process as claimed inclaim 4, wherein the formaldehyde source is used in such an amount that1.3 to 1.45 molar equivalents of formaldehyde are available.
 6. Aprocess as claimed in claim 1, wherein, to recover theN-phosphonomethyliminodiacetic acid, the pH of the reaction mixture isbrought to not more than 1.3 by adding a base.
 7. A process as claimedin claim 6, wherein the pH is brought to 0 to 0.8.
 8. A process asclaimed in claim 6, wherein 5 to 25% by weight strength sodium hydroxidesolution is used as the base.